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Construction of Streptomyces coelicolor A3(2) mutants that exclusively produce NA4/NA6 intermediates of agarose metabolism through mutation induction.
Kim, Jina; Kim, Eun Joo; Ko, Hye-Jeong; Lee, Yeon-Hee; Hong, Soon-Kwang; Shin, Miyoung; Lee, Je Hyeon; Kwak, Woori.
Afiliación
  • Kim J; Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.
  • Kim EJ; Dyne Bio Inc., Seongnam-si, Gyeonggido, 13209, Republic of Korea.
  • Ko HJ; Dyne Bio Inc., Seongnam-si, Gyeonggido, 13209, Republic of Korea.
  • Lee YH; Dyne Bio Inc., Seongnam-si, Gyeonggido, 13209, Republic of Korea.
  • Hong SK; Department of Biological Science and Bioinformatics, Myongji University, 116 Myongji-Ro, Cheoin-gu, Yongin, 17058, Gyeonggido, Korea.
  • Shin M; Department of Pathology, Yale University School of Medicine, New Haven, CT, 06510, USA.
  • Lee JH; Dyne Bio Inc., Seongnam-si, Gyeonggido, 13209, Republic of Korea. jhl@dynebio.co.kr.
  • Kwak W; Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. woori@catholic.ac.kr.
Sci Rep ; 13(1): 18968, 2023 11 03.
Article en En | MEDLINE | ID: mdl-37923760
NA4/NA6, an intermediate degradation product of ß-agarase, is a high value-added product with anticancer, anti-obesity, and anti-diabetic effects. Therefore, a method that enables the efficient production of NA4/NA6 would be useful from economic and medical perspectives. In this study, we aimed to generate a Streptomyces coelicolor A3(2) mutant M22-2C43 that produces NA4/NA6 as a final product; this method serves as a more efficient alternative to the enzymatic conversion of ß-agarase for the generation of these products. The M22-2C43 strain was generated through two rounds of mutagenesis and screening for increased ß-agarase activity and effective production of NA4/NA6. We assembled the complete genomes of two mutants, M22 and M22-2C43, which were identified following a two-round screening. Large and small genetic changes were found in these two mutants, including the loss of two plasmids present in wild-type S. coelicolor A3(2) and chromosome circularization of mutant M22-2C43. These findings suggest that mutant M22-2C43 can produce NA4/NA6 as a degradation product due to functional inactivation of the dagB gene through a point mutation (G474A), ultimately preventing further degradation of NA4/NA6 to NA2. To our knowledge, this is the first report of a microbial strain that can effectively produce NA4/NA6 as the main degradation product of ß-agarase, opening the door for the use of this species for the large-scale production of this valuable product.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Streptomyces coelicolor Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Streptomyces coelicolor Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido